rs16906205

Variant names:

• chr11-49199503-G-C
• rs16906205
• NM_004476.3:c.411+752C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-49199503-G-C
• chr11-49199503-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004476.3(FOLH1):​c.411+752C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,176 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.071 (431 hom., cov: 32)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 3 publications found

Genes affected

FOLH1 (HGNC:3788): (folate hydrolase 1) This gene encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. The protein acts as a glutamate carboxypeptidase on different alternative substrates, including the nutrient folate and the neuropeptide N-acetyl-l-aspartyl-l-glutamate and is expressed in a number of tissues such as prostate, central and peripheral nervous system and kidney. A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. In the prostate the protein is up-regulated in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants encoding several different isoforms. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.411+752C>G		intron_variant	Intron 3 of 18	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.411+752C>G		intron_variant	Intron 3 of 18	1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10724 AN: 152058 Hom.: 429 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0727

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0705 AC: 10736 AN: 152176 Hom.: 431 Cov.: 32 AF XY: 0.0692 AC XY: 5150 AN XY: 74392

African (AFR) AF: 0.0392 AC: 1627 AN: 41506

American (AMR) AF: 0.0665 AC: 1017 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3468

East Asian (EAS) AF: 0.0944 AC: 489 AN: 5182

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4820

European-Finnish (FIN) AF: 0.0624 AC: 661 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0914 AC: 6213 AN: 67996

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0319 Hom.: 15

Bravo AF: 0.0711

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.1
DANN	Benign	0.72
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16906205; hg19: chr11-49221055;